The invention relates to a non-invasive method for measuring the volume, the composition and the movement of electroconductive body fluids, based on the electrical impedance of the body or a body segment, especially for performing electromechanocardiography (ELMEC) or impedance cardiography (IKG) measurements for determining hemodynamic parameters, wherein an alternating measuring current of at least one frequency is introduced into the body by measuring electrodes applied to the body surface.
In medical practice, it is often necessary to measure cardiac mechanical activity. There are different methods, such as echocardiography, for measuring stroke force, inotropism, contractility and ejection fraction. In addition, the amount of blood a heart ejects in one heartbeat, stroke volume and other hemodynamic parameters are frequently determined. If the heart rate is known, cardiac output (cardiac output=cardiac output per minute=CO) may thus be calculated. From these values cardiac function may be derived, which in turn is a basis for the diagnosis of heart diseases and new physiological findings. However, echocardiography is not really appropriate for monitoring patients with serious heart diseases in ICUs or during anesthesia because it requires the permanent presence of medical personnel. Since this constitutes a serious problem, medics have numerous other methods at their disposal for determining CO.
One such method comprises the introduction of a catheter into the pulmonary artery and/or into the aorta, where by means of an indicator value or substance, which may be heat, cold, sodium chloride or lithium, a drop of said indicator substance within a measuring distance may be determined, followed by the determination of CO according to the Fick principle. A disadvantage of this method concerns the introduction of a catheter into a human vessel and complications resulting therefrom, such as bleeding and infections. Consequently, this invasive method involves high costs with regard to disposable catheters and high risks for patients. See Dalen, J. E, “The Pulmonary Artery Catheter—Friend, Foe, or Accomplice?” JAMA, 286(3): 348-350 (Jul. 18, 2001); Polanczyk C. A. et al., “Right Heart Cathertization and Cardiac Complications in Patients Undergoing Noncardiac Surgery” JAMA, 286(3): 309-314 (Jul. 18, 2001). The principle of thermodilution or dye dilution is also susceptible to errors so that usually an average of several measurements is required to obtain a plausible result. Furthermore, physical strain or other conditions resulting in body temperature variations also yield wrong results in thermodilution.
Recently it has been attempted to use the Flick principle to determine cardiac output by measuring gases in alveolar air. This is made possible by the quick gas exchange between blood and alveolar air so that the concentration in these two media can practically be equated. If a gas is added to alveolar air, its blood concentration increases as well, and if the gas addition is stopped, gas content decreases in the blood as well as in the alveolar air, wherein according to the Fick principle, CO can be calculated from the concentration decrease within a given time unit.
One method that has proven especially successful is CO2 rebreathing. Here, a loop is introduced into the patient's respiratory tract, and the patient rebreathes his own exhaled air for a particular period of time to increase CO2 concentration in the blood. A disadvantage of this method is that the patient has to wear a mouthpiece and keep his respiration rather steady to guarantee a constant concentration of breathing gases in the alveolar air and the blood. Therefore, this method is mainly used during anesthesia which guarantees a steady tidal volume and a steady respiratory rate. With spontaneously breathing patients, there remains the disadvantage of respiration through a tube system with a mouthpiece, which considerably increases respiratory dead space and airway resistance, and consequently also breathing effort. Furthermore, the method's accuracy decreases significantly with spontaneous breathing. Another method for measuring CO consists in a similar technique where instead of CO2 an inert gas is used, which is inhaled and also quickly equilibrates in the blood.
Another method involves the determination of stroke volume and other hemodynamic parameters from the pulse form, which is sensed at a peripheral artery. Pulse form variations are partly due to changes of stroke volume and other hemodynamic parameters, which allows an indirect derivation of changes of stroke volume and other hemodynamic parameters by means of a transfer function. This method, however, requires calibration by one of the above techniques at the beginning and is not sufficiently accurate. Another well-known method relates to the transcutaneous measurement of an indicator substance, such as indigo green, at the capillaries of an ear or finger, which, however, significantly reduces the accuracy of the Fick principle.
Another method well known in the art is impedance cardiography (IKG). In this method, a constant alternating electric field is applied to the thorax, and the alternating voltage variation caused by the alternating electric field indicates a change of thoracic fluid content. More particularly, with this method resistance to alternating current (impedance) is measured, which is a measure for the change of thoracic fluid content. The change of the thoracic fluid content, on the other hand, is a measure for the amount of blood ejected per stroke. From stroke volume and other hemodynamic parameters (SV) and the heart rate (HR), cardiac output (CO=SV*HR) can be calculated.
Usually a pair of electrodes leading a current to the body is attached above or at the upper limit and below or at the lower limit of the thorax. Between this pair of electrodes, a second pair of electrodes is attached for measuring the resulting alternating current. The inner pair of electrodes must be kept at a particular distance so that the upper voltage electrode is positioned at least at glottis level, and the lower electrode at xiphoid level. The distance between the two electrodes also depends on the thorax length and is hereafter called electrode measuring length L. Impedance is calculated according to the following formula: Z(t)=u(t)/I0, where u(t) is the changing alternating current and I0 is the alternating current constant effective current intensity impressed into the body.
So far, either circular electrodes or spot electrodes similar to ECG electrodes have been used for this purpose. Austrian patent application A 392/2001, filed on Mar. 13, 2001, by J. Fortin et al. for “Medical Electrode” describes a new electrode arrangement, where two strip electrodes run parallel to each other over a short distance on the same sheet, their distance from each other being exactly preset by the common carrier sheet and reproducible. One of these parallel strip electrodes mounted on the common carrier sheet serves for the application of the measuring current, the other parallel strip electrode is intended for sensing the measuring voltage. The upper pair of electrodes (or double electrode) can be positioned, for example, at the neck, the lower pair of electrodes left and right, respectively, at the inferior thoracic aperture. This electrode arrangement shows much better reproducibility of results than former circular electrodes and the spot electrodes described in the U.S. Pat. No. 4,450,527 of Sramek for “Noninvasive Continuous Cardiac Output Monitor,” see FIG. 1a+FIG. 1b. 
Disadvantages of the above impedance technique relate to the fact that the results are calculated according to the Kubicek equation (Kubicek, W. G., et al., “Development and Evaluation of an Impedance Cardiac Output System,” Aerospace Medicine 37, 1208-1212 (1966); and “The Minnesota Impedance Cardiograph—Theory and Applications,” Biomed. Eng., 9(2): 410-416 (1974)) or the Sramek equation (U.S. Pat. No. 4,450,527 of Sramek et al.; Sramek, B., “Noninvasive Continuous Cardiac Output Monitor”; Sramek, B., “Noninvasive Technique for Measurement of Cardiac Output by Means of Electrical Impedance,” Proceedings of the Vth ICEBI, Tokyo (1981); and Sramek, B. et al., “Stroke Volume Equation with a Linear Base Impedance Model and Its Accuracy, as Compared to Thermodilution and Magnetic Flowmeter Techniques in Humans and Animals, Proceedings of the Vth ICEBI, Zadar, Yugoslavia, p. 38 (1983)), respectively, both being based on strongly simplified assumptions about the human body. These assumptions are only partly true, which leads to considerable errors in the calculation of stroke volume and other hemodynamic parameters as well as of cardiac output.
Equation 1 shows the Kubicek equation for calculating stroke volume and other hemodynamic parameters from a variation of the impedance signal:
                    SV        =                  ρ          *                                                    L                2                                            Z                0                2                                      ·            LVET            ·                                          (                                                      ⅆ                    Z                                    /                                      ⅆ                    t                                                  )                            max                                                          (        1        )            Herein, L is the measuring length in cm between two electrodes on the body surface, ρ is the resistivity of the blood in Ω cm, Z0 is the base impedance in Ω, (dZ/dt)max is the maximum of the first derivative of electrical resistance and impedance variations with respect to time in Ω/sec by cardiac activity and LVET, left ventricular ejection time in sec.
As can be seen, the electrode measuring length L enters the equation as a quadratic value, wherein, at present, this electrode measuring length is determined on the thorax surface.
Furthermore, blood resistivity ρ is a linear value in the formula, which means that blood resistivity mainly depends on the blood's content of red blood cells. According to the law by Lamberts, R. et al., “Impedance Cardiography,” Van Gorcum, Assen, Holland (1984)], ρ can be approximately calculated from the hematocrit Hct by means of the formulaρ=71.24.e0.000358 Hct power 2  (2)or estimated by means of a similar formula or, in other methods, simply kept constant. What is not taken into account here is that blood conductivity is not only influenced by the hematocrit, but also by the ionic concentration in plasma as well as proteins contained therein. Therefore, an empirically determined equation, which takes into account only one and not all blood components, will never give the exact conductivity or resistance of blood. Furthermore, blood conductivity is also influenced by the flow rate, since with higher velocity erythrocytes are oriented lengthwise and consequently increase fluid cross section. With even higher velocities and resulting turbulences, blood resistance can increase even further.
The formula according to Sramek uses 17% of standing height instead of the electrode measuring length, since it has been empirically shown that thorax length corresponds approximately to 17% of total body length. Another assumption in this formula is the divisor 4.25, which arises from an estimated relation between electrode measuring length and waist circumference as well as an estimated constant relation between a cylindrical thorax model and a truncated-cone thorax model (see U.S. Pat. No. 4,450,527, column 5, line 50ff). Body length H therefore even enters the formula as a cubic value.
                    SV        =                                                            (                                  0.17                  ·                  H                                )                            3                        4.25                    ·          LVET          ·                                                    (                                                      ⅆ                    Z                                    /                                      ⅆ                    t                                                  )                            max                                      Z              0                                                          (        3        )            
Bernstein, D. P. et al. (see “A New Stroke Volume Equation for Thoracic Electrical Bioimpedance: Theory and Rationale,” Critical Care Medicine, 14: 904 to 909 (1986)) “corrected” this formula by multiplying the above formula by a correction factor δ.δ=β(Wreal/Wideal)  (4)wherein β is a blood volume index, and Wideal and Wreal are the ideal and real weights of an individual.
The ideal weight for men isW ideal=0.534H−17.36  (5)
The ideal weight for women isW ideal=0.534H−27.36  (6)Herein, H is the standing height in cm.
This shows that in all equations different measuring units are mixed. Consequently, the resulting equations have nothing to do with correctly derived, credible mathematics. By introducing anthropometric values into such an equation, indirect measures for stroke volume and other hemodynamic parameters of the heart of healthy individuals are directly involved in the calculation of stroke volume and other hemodynamic parameters. In individuals with healthy hearts, CO shows a perfect relation to the body surface. Consequently, the formula contains a parameter which has nothing to do with the measurement of stroke volume and other hemodynamic parameters, i.e. the patient's body measurements. Based on standing height and resulting electrode measuring length L between glottis and xiphoid, tall patients therefore automatically have larger stroke volumes and higher other hemodynamic parameters than small patients. The above formula by KUBICEK directly includes a measure for body dimensions as well.
As shown in FIG. 1, the measuring length between the electrodes, when placed correctly between the superior and inferior thoracic apertures, correlates surprisingly well with the patient's height.
According to the above, in individuals without heart diseases, hemorrhagically measured stroke volume and other hemodynamic parameters correspond well with impedance cardiography results because real standing height is a measure for cardiac output. A tall and heavy individual actually has to transport much more blood to tissue within a certain time unit than a delicate individual. With heart diseases, this principle does not hold anymore so that the correlation between actual cardiac output and cardiac output measured by impedance cardiography is bad or not existent because body measurement values introduced into the formula loose their significance. In individuals with heart diseases, this leads to an enormous bias towards normal and thus incorrect high values.
Additionally, values determined by impedance cardiography are distorted in the wrong direction, that is towards too high CO values, because of the following phenomenon. Due to their illness, patients with cardiac insufficiency usually have more body fluid in their thorax than individuals with healthy hearts. The increased thoracic fluid content reduces base impedance Z0 in Q by nature. This value enters the respective calculation formula in an inverted (Sramek) or quadratically inverted form and gives CO values that are too high, which can lead to fatal diagnostic errors. In individuals with healthy hearts, Z0 is a measure for thorax geometry, which is not the case in patients with increased thoracic fluid content.
This is illustrated in FIG. 2. Here the ejection fraction EF was measured echocardiographically according to the Simpson technique in patients with and without cardiac insufficiency and compared with CO. The echocardiographic parameter EF was used instead of echocardiographically measured CO because this value can be determined much more accurately. As can be seen, there is no relation between CO and ejection fraction, a relation that would, however, be expected to exist if impedance cardiography was a suitable method for cardiac insufficiency.
Consequently, impedance cardiography has not really become accepted by cardiologists, at least in Europe, because correspondence with the actual stroke volume and other hemodynamic parameters may be good in individuals with healthy hearts, but in individuals with heart diseases, where the results are really decisive for diagnosis, accurateness is rather poor. In the United States, the technique has nevertheless been increasingly used because it has been shown that relative changes of stroke volume and other hemodynamic parameters can thereby be monitored rather conveniently so that effects of pharmacological interventions can be determined very well, even if the absolute values are wrong.
Furthermore, none of the apparatus currently available on the market is able to provide results for stroke volume and other hemodynamic parameters or CO without first entering standing height or thorax length between the electrodes, i.e. a different measure for standing height. Especially in intensive care units, a patient's weight and height can often not be measured or asked for. Entering a wrong value, which in practice can happen easily, would even further distort the results.
An apparatus or a method for measuring cardiac output should, however, be able to give reliable results without a priori knowledge about standing height and weight, as is the case with the gold standard of thermodilution and other methods using the Fick principle, for example the CO2 rebreathing technique or other breathing gas methods. As soon as a priori knowledge about body measurements is used, the measuring results are pushed into the direction where the CO value should be, i.e., a bias is introduced into the equation that simulates good results of the respective method in individuals with healthy hearts. Furthermore, in case of electrically measured cardiac output only electrically measured parameters should be introduced into an equation.
U.S. Pat. No. 4,450,527 describes an apparatus for impedance measurements where the dimensions of the thorax, especially the measuring length between the electrodes, where the measurements are conducted, have to be determined and entered. Thorax impedance is measured as a function of time and effects caused by respiration movements are eliminated so that the patient can breath normally during the measurement process. Spot electrodes for current impression as well as sensing of a measuring voltage are positioned in the neck area and sternum area. The measuring length between the lower and upper electrodes is not changed during the measurement.
U.S. Pat. No. 5,109,870 describes a catheter for measuring motility and peristalsis in tubular organs, e.g. the esophagus, by simultaneous, multiple impedance measurements, which catheter includes an insulating plastic tube, annular electrodes and interior channels for electrode leads. The annular electrodes are connected to impedance transformers which convert the measured signals into voltage or current signals so that they can be displayed. Due to this multiple electrode arrangement a simultaneous measurement of a plurality of measuring channels is possible in order to draw conclusions with regard to movement and transport characteristics of the organ being measured. For this purpose the catheter has to be inserted into the organ and fixed therein in a particular position. Even for patients in good health condition, this measuring method is rather strenuous and can therefore not be repeated arbitrarily often. Cardiac output is not determined with said method.
U.S. Pat. No. 4,951,682 discloses a cardiac catheter for measuring cardiac output by means of a plurality of spaced ring electrodes. In the introduction (column 2, second paragraph), this document mentions non-invasive techniques for obtaining cardiac output and holds that these have severe limitations and that invasive measurements by means of cardiac catheters show decisive advantages. Only invasive cardiac catheter measurements are mentioned, which by nature cannot be repeated very often on one patient and may entail serious complications.
U.S. Pat. No. 4,947,862 describes a device for the measurement of the amount of body fat on a patient by a applying high-frequency current to the body and sensing a voltage. It comprises magnitude and phase detection circuits for measuring the magnitude and phase of the produced voltage signals with reference to the impressed current. Here, standing height, weight and age have to be determined and entered into an input device, wherein measuring errors relating to these values enter the calculation of the amount of body fat.
Finally, U.S. Pat. No. 5,063,937 discloses a multiple frequency measurement system for determining bioimpedance of a patient's body over a large frequency range, wherein errors in the determination of the measuring length between the electrodes are not taken into consideration.